Babies born too early can have health-related risks during their first years of life. Scientists are looking into frequent and significant problems in infants. They think that poor growth following premature birth could be due to malnutrition and stress during pregnancy. Several studies have found a link between fetal malnutrition, low birth weight and low muscle mass and strength throughout life.


“It’s important to know how the muscles of the fetus are affected because we need muscles to breathe, eat, swallow and move,” said Dr. Marta Fiorotto, associate professor of pediatrics-nutrition and of molecular physiology and biophysics at the USDA/ Children’s Nutrition Research Center at Baylor College of Medicine and Texas Children’s Hospital, where the research was performed.

“If these muscles are compromised in any way during fetal development, these functions can also likely to be compromised in newborns and affect their growth later.” Scientists recommend that malnutrition and stress are the two main environmental factors that affect fetal growth. Interestingly, these two factors cause the fetus to have high levels of cortisol, an endogenous glucocorticoid, which is a class of stress steroid hormone.

“Lack of proper nutrition is a form of stress in pregnant women and lead to raising the levels of cortisol in the blood.” said Fiorotto, director of the Mouse Metabolic Research Unit at the USDA/ARS Children’s Nutrition Research Center at Baylor and Texas Children’s Hospital.

“We want to know whether it was the lack of proper nutrition during pregnancy or the exposure to high levels of glucocorticoids that affect fetal development. In adults, glucocorticoids have negative effects on muscles, for example, they cause muscle atrophy and increase insulin resistance. Why would the newborn be any different?” Dr. Ganga Gokulakrishnan, a neonatologist at Texas Children’s Hospital and assistant professor at Baylor College of Medicine, in collaboration with Dr. Fiorotto, and colleagues have discovered how glucocorticoids affect the growth of fetal muscles in the rat.

“You can think of a muscle as uncooked spaghetti; each spaghetti is a fiber – a single muscular cell – with many nuclei in a matrix of protein. The number of fibers has been determined at birth and has not increased during postnatal life.” Dr. Gokulakrishnan said.

So, postnatally, muscles grow by adding both more protein and more nuclei to the fibers. Nuclei are added by muscle stem cells, also called satellite cells that divide and fuse with the fibers.” “These muscle stem cells drive muscle growth during fetal development. After puberty, however, the muscles stop accumulating nuclei and grow by adding only protein to the fibers.”

Previous studies in rats have shown that exposing fetuses to glucocorticoids impairs muscle growth and that this is due in part to reduced protein production. In this study, Gokulakrishnan and the colleagues examined the effect of glucocorticoids on the other mechanism of muscle growth, namely the addition of nuclei to the fibers by satellite cells, during early development.


“We were surprised at the magnitude of impairment we observed in the replication of satellite cells in the muscles of fetal rats exposed to glucocorticoids,” said Gokulakrishnan. “Taking all the results together, we found that the effect of glucocorticoids on fetal muscle growth is quite complex; it depends on the duration, the level of glucocorticoids and the time during pregnancy when it occurs.”

The researcher’s highlights that when the level of stress is mild, such as when the mother’s food intake is only approximately 85 percent of normal, protein deposition in the muscles of the fetus is affected quite remarkably. However, this mild restriction in food intake does not affect the accumulation of nuclei. 

“Our results from the current study indicate that treating rats with a dose of glucocorticoids that mimics more severe food restriction affects the reserve of satellite cells, the accumulation of nuclei in the fibers, and therefore, muscle growth. The health of future generations starts with the health of the mother. In short, maternal stress, due to malnutrition or other causes that increase the exposure of her fetus to glucocorticoids, can significantly affect the growth of fetal muscles,” Gokulakrishnan said. 

“Problems such as stress or malnutrition are factors that could be identified and mitigated by prenatal care, once again emphasizing the importance of a proper diet and antenatal care for all pregnant moms.” “Maternal stress negatively affects the growth of the fetus at the cellular level. This has been demonstrated for other organs, including the brain,” said Fiorotto. “We have now learned that, because this is affecting muscle stem cells, it is possible that these negative effects on the fetus could have life-long consequences. This is another example that illustrates how the health of future generations starts with the health of the mother.”

This study also brings the effects of glucocorticoids on the fetus into play when considering treating expecting mothers or newborn babies with steroids for a medical condition. In addition, ongoing research is determining whether the deleterious effects on the fetus can be minimized or eliminated by medical intervention after birth.


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